Overexpression of 15-Hydroxyprostaglandin Dehydrogenase Inhibits A549 Lung Adenocarcinoma Cell Growth via Inducing Cell Cycle Arrest and Inhibiting Epithelial-Mesenchymal Transition

Bladder cancer (BCa) is one of the most common tumors, but its underlying mechanism has not been fully clarified. Our transcriptome analysis suggested a close link of Sirtuins, Peroxisome Proliferator-Activated Receptor (PPAR), cell cycle regulation, reactive oxygen species (ROS) metabolism, and Forkhead Box Class O (FOXO) signaling pathway in BCa. SIRT1 is a key member of Sirtuins, playing important roles in aging and energy metabolism, which has been reported to be involved in various metabolic diseases and tumors. We observed that SIRT1 was upregulated in BCa tissues at both mRNA and protein levels. By establishing a SIRT1-knockdown BCa cell model, our results suggested that proliferation and viability were suppressed. Moreover, migration rate was inhibited as well, possibly via reduction of epithelial-mesenchymal transition (EMT). In addition, cell cycle arrest was significantly induced, consisting with strongly decreased proteins involved (CDK2/4/6). Furthermore, ROS production was slightly reduced, accompanied by increasing of antioxidant enzymes and total/acetylated FOXO3a. Consistently with our Path-net analysis, we observed no significant alteration of apoptosis in the SIRT1-knockdown BCa cells. Taken together, our results suggested that SIRT1 deficiency in BCa cells could suppress cell viability by activating antioxidant response and inducing cell cycle arrest possibly via FOXO3a-related pathways.

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Association of cell cycle arrest with anticancer drug-induced epithelial-mesenchymal transition in alveolar epithelial cells

Toxicology ◽

10.1016/j.tox.2019.06.002 ◽

2019 ◽

Vol 424 ◽

pp. 152231 ◽

Cited By ~ 2

Author(s):

Masashi Kawami ◽

Risako Harada ◽

Takamichi Ojima ◽

Yohei Yamagami ◽

Ryoko Yumoto ◽

...

Keyword(s):

Cell Cycle ◽

Epithelial Cells ◽

Cell Cycle Arrest ◽

Anticancer Drug ◽

Epithelial Mesenchymal Transition ◽

Alveolar Epithelial Cells ◽

Drug Induced ◽

Mesenchymal Transition ◽

Alveolar Epithelial ◽

Cycle Arrest

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Snai1-induced partial epithelial–mesenchymal transition orchestrates p53–p21-mediated G2/M arrest in the progression of renal fibrosis via NF-κB-mediated inflammation

Cell Death and Disease ◽

10.1038/s41419-020-03322-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ruochen Qi ◽

Jiyan Wang ◽

Yamei Jiang ◽

Yue Qiu ◽

Ming Xu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Renal Fibrosis ◽

Epithelial Mesenchymal Transition ◽

Interstitial Fibrosis ◽

Ischemia Reperfusion ◽

Underlying Mechanism ◽

Mesenchymal Transition ◽

Cycle Arrest ◽

Renal Fibrogenesis

AbstractRenal fibrosis is the common feature of all progressive kidney diseases and exerts great burden on public health worldwide. The maladaptive repair mechanism of tubular epithelial cells, an important mediator of renal fibrogenesis, manifests with partial epithelial–mesenchymal transition (EMT) and cell cycle arrest. The aim of this study is to investigate the possible correlation between partial EMT and cell cycle arrest, and elucidate the underlying mechanism. We examined human kidney allograft samples with interstitial fibrosis and three mice renal fibrosis models, unilateral ureter obstruction (UUO), ischemia–reperfusion injury, and Adriamycin nephropathy. The partial EMT process and p53–p21 axis were elevated in both human allograft with interstitial fibrosis, as well as three mice renal fibrosis models, and showed a time-dependent increase as fibrosis progressed in the UUO model. Snai1 controlled the partial EMT process, and led to parallel changes in renal fibrosis, G2/M arrest, and inflammation. p53–p21 axis arrested cell cycle at G2/M, and prompted partial EMT and fibrosis together with inflammation. NF-κB inhibitor Bay11-7082 disrupted the reciprocal loop between Snai1-induced partial EMT and p53–p21-mediated G2/M arrest. We demonstrated the reciprocal loop between partial EMT and G2/M arrest of TECs during renal fibrogenesis and revealed NF-κB-mediated inflammatory response as the underlying mechanism. This study suggests that targeting NF-κB might be a plausible therapeutic strategy to disrupt the reciprocal loop between partial EMT and G2/M arrest, therefore alleviating renal fibrosis.

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